crossing96/oncoscreening huggingface dataset:
Insight into bladder cancer care: study protocol of a large nationwide prospective cohort study (BlaZIB).	BACKGROUND: Despite the embedding of bladder cancer management in European guidelines, large variation in clinical practice exists for applied diagnostics and treatments. This variation may affect patients' outcomes including complications, disease recurrence, progression, survival, and health-related quality of life (HRQL). Lack of detailed clinical data and HRQL data hampers a comprehensive evaluation of bladder cancer care. Through prospective data registration, this study aims to provide insight in bladder cancer care in the Netherlands and to identify barriers and modulators of optimal bladder cancer care. METHODS: This study is a nationwide prospective cohort study including all patients who were newly diagnosed with high-risk non-muscle invasive bladder cancer (HR-NMIBC; Tis and/or T1, N0, M0/x) or non-metastatic muscle invasive bladder cancer (MIBC; ≥T2, N0/x-3, M0/x) in the Netherlands between November 1st 2017 and October 31st 2019. Extensive data on patient- and tumor characteristics, diagnostics, treatment and follow-up up to 2 years after diagnosis will be collected prospectively from electronic health records in the participating hospitals by data managers of the Netherlands Cancer Registry (NCR). Additionally, patients will be requested to participate in a HRQL survey shortly after diagnosis and subsequently at 6, 12 and 24 months. The HRQL survey includes six standardized questionnaires, e.g. SCQ Comorbidity score, EQ-5D-5 L, EORTC-QLQ-C30, EORTC-QLQ-BLM30, EORTC-QLQ-NMIBC24 and BCI. Variation in care and deviation from the European guidelines will be assessed through descriptive analyses and multivariable multilevel analyses. Survival analyses will be used to assess the association between variation in care and relevant outcomes such as survival. DISCUSSION: The results of this observational study will guide modifications of clinical practice and/or adaptation of guidelines and may set the agenda for new specific research questions in the management of bladder cancer. TRIAL REGISTRATION: Retrospectively registered in the Netherlands Trial Register. Trial identification number: NL8106. Registered on October 22nd 2019.	bladder
The clinicopathological and prognostic value of CD44 expression in bladder cancer: a study based on meta-analysis and TCGA data.	CD44 is reported to be involved in tumor invasion and metastasis. However, the role of cancer stem cell marker CD44 in bladder cancer still remains controversial. Hence, the correlations between CD44 expression and the clinicopathological features and the prognosis of bladder cancer were investigated. Publications using immunohistochemical methods were identified. The Cancer Genome Atlas (TCGA) data were also analyzed. The odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were calculated. 14 studies involving 1107 tissue samples were included. CD44 expression in bladder cancer was lower than in non-tumor tissue samples (OR = 0.14, P = 0.005), which was consistent with TCGA data. CD44 expression was correlated with advanced T stage (OR = 1.76, P = 0.029) and lymph node metastasis (OR = 4.09, P < 0.001). Multivariate survival analysis showed that CD44 expression was not linked to tumor-specific survival, overall survival, and recurrence/relapse-free survival, but was associated with disease failure (HR = 2.912, 95% CI = 1.51-5.61). No relationships of CD44 expression with the clinicopathological features and overall survival were found from TCGA data. Our finding suggested that CD44 expression may be correlated with progression, metastasis, and disease failure of bladder cancer. However, further large-scale studies are needed.Abbreviations: CD44: Cluster of Differentiation 44; CIs: Confidence Intervals; CSCs: Cancer Stem Cells; EMT: Epithelial-mesenchymal Transition; HRs: Hazard Ratios; ORs: Odds Ratios; TCGA: The Cancer Genome Atlas.	bladder
Disseminated Bacillus Calmette-Guérin Infection Detected on FDG PET/CT Following Intravesical Bacillus Calmette-Guérin Therapy.	We report the case of a 64-year-old man who presented with back pain, anorexia, and weight loss 9 months following bacillus Calmette-Guérin immunotherapy for high-grade transitional cell carcinoma of the bladder. A FDG PET/CT was performed, which demonstrated osteolysis and intense FDG avidity of the T6/T7 and T8/T9 vertebral endplates. In addition, an aneurysm with FDG-avid soft tissue was present of the distal left common iliac artery. The provisional diagnosis was disseminated bacillus Calmette-Guérin infection, resulting in spondylodiscitis and a mycotic aneurysm. A CT-guided vertebral biopsy confirmed the presence of Mycobacterium tuberculosis DNA on polymerase chain reaction testing.	bladder
Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer.	PD-1 and PD-L1 act to restrict T cell responses in cancer and contribute to self-tolerance. Consistent with this role, PD-1 checkpoint inhibitors have been associated with immune-related adverse events (irAEs), immune toxicities thought to be autoimmune in origin. Analyses of dermatological irAEs have identified an association with improved overall survival (OS) following anti-PD-(L)1 therapy, but the factors that contribute to this relationship are poorly understood. We collected germline whole-genome sequencing data from IMvigor211, a recent phase 3 randomized controlled trial comparing atezolizumab (anti-PD-L1) monotherapy to chemotherapy in bladder cancer. We found that high vitiligo, high psoriasis, and low atopic dermatitis polygenic risk scores (PRSs) were associated with longer OS under anti-PD-L1 monotherapy as compared to chemotherapy, reflecting the Th17 polarization of these diseases. PRSs were not correlated with tumor mutation burden, PD-L1 immunohistochemistry, nor T-effector gene signatures. Shared genetic factors impact risk for dermatological autoimmunity and anti-PD-L1 monotherapy in bladder cancer.	bladder
Early life body size and its associations with adult bladder cancer.	Background: Adult overweight is a potential bladder cancer (BC) risk factor, but little is known about size earlier in life.Aim: To investigate if birth weight, childhood body mass index (BMI), height and growth are associated with adult BC.Subjects and methods: Anthropometric information from birth and ages 7-13 on 315,763 individuals born 1930-1989 in the Copenhagen School Health Records Register was linked to national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression.Results: 1145 individuals (839 men) were diagnosed with BC. Sex differences were not detected. Childhood BMI had positive associations and height had inverse associations with BC; at age 13, HR = 1.10 (95% CI: 1.02-1.18) per BMI z-score and HR = 0.94 (95% CI: 0.89-1.00) per height z-score. A pattern of above-average increases in BMI from 7 to 13 years had higher hazards of BC than average increases. Above-average growth in height was not significantly associated with BC. Compared with birth weights of 3.5 kg, low (2.5 kg) and high (4.5 kg) values were associated with increased hazards of BC; HR = 1.26 (95% CI: 1.01-1.58) and HR = 1.36 (95% CI: 1.09-1.70), respectively.Conclusions: A high BMI, a short height, excess BMI gain in childhood and low and high birth weights are associated with increased hazards of BC.	bladder
Tissue stiffness contributes to YAP activation in bladder cancer patients undergoing transurethral resection.	Changes in the cellular microenvironment play a critical role in the development of bladder cancer (BC). Yes-associated protein (YAP), a central mediator of the Hippo pathway, functions as a nuclear sensor of mechanotransduction that can be induced by stiffness of the extracellular matrix (ECM), including stiffness resulting from surgical manipulations. We aimed to clarify the possible association between surgically-related ECM stiffness and YAP activation in BC patients. We compared 30 bladder cancer tissues with grade II (n = 15 recurrent and n = 15 newly diagnosed) with 30 adjacent healthy tissues. Atomic force microscopy showed that patients with recurrent BC had stiffer ECM than newly diagnosed patients (P < 0.05). Gene expression profiles showed that β1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, β1 integrin activation was confirmed using a specific antibody. Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery-induced ECM stiffness can influence integrin-FAK-YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.	bladder
Critical role of SOX2-IGF2 signaling in aggressiveness of bladder cancer.	Signaling elicited by the stem cell factors SOX2, OCT4, KLF4, and MYC not only mediates reprogramming of differentiated cells to pluripotency but has also been correlated with tumor malignancy. In this study, we found SOX2 expression signifies poor recurrence-free survival and correlates with advanced pathological grade in bladder cancer. SOX2 silencing attenuated bladder cancer cell growth, while its expression promoted cancer cell survival and proliferation. Under low-serum stress, SOX2 expression promoted AKT phosphorylation and bladder cancer cells' spheroid-forming capability. Furthermore, pharmacological inhibition of AKT phosphorylation, using MK2206, inhibited the SOX2-mediated spheroid formation of bladder cancer cells. Gene expression profiling showed that SOX2 expression, in turn, induced IGF2 expression, while SOX2 silencing inhibited IGF2 expression. Moreover, knocking down IGF2 and IGF1R diminished bladder cancer cell growth. Lastly, pharmacological inhibition of IGF1R, using linsitinib, also inhibited the SOX2-mediated spheroid formation of bladder cancer cells under low-serum stress. Our findings indicate the SOX2-IGF2 signaling affects the aggressiveness of bladder cancer cell growth. This signaling could be a promising biomarker and therapeutic target for bladder cancer intervention.	bladder
Expression of cancer stem cells markers in urinary bladder urothelial carcinoma and its precursor lesions.	BACKGROUND: Cancer stem cells (CSC) and their role in tumorigenesis of various solid tumors have been studied in past decades. Urothelial CSC were first identified 10 years ago and subsequent studies have been performed with the aim to identify reliable markers of CSC. So far, a few studies have investigated a relationship between CSC markers expression in urothelial carcinoma tissue and histopathological characteristics of the tumor. METHODS: In our study, we evaluated an immunoexpression of the CSC markers CD24, CD44, CD66 and CD133 in tissue sections of urothelial carcinoma (all tumor grades and stages were included), urothelial carcinoma in situ and non-neoplastic urothelium, totally 218 specimens were enrolled. RESULTS: All studied molecules were expressed either in tumor tissue and non-neoplastic urothelium. Urothelial carcinomas of higher tumor grade and stage expressed molecules CD24 and CD133 significantly more frequently whereas molecules CD44 and CD66 did not show significant association with tumor histopathological features. CONCLUSIONS: Our results showed that studied molecules are not suitable for direct detection of CSC in urothelial carcinoma tissue sections, but an expression of molecules CD24 and CD133 is significantly related to urothelial carcinoma grade and stage, which are both important prognostic indicators and therefore an expression of these markers might have a potential prognostic value.	bladder
Identification of Prognostic Immune Genes in Bladder Urothelial Carcinoma.	BACKGROUND: The aim of this study is to identify possible prognostic-related immune genes in bladder urothelial carcinoma and to try to predict the prognosis of bladder urothelial carcinoma based on these genes. METHODS: The Cancer Genome Atlas (TCGA) expression profile data and corresponding clinical traits were obtained. Differential gene analysis was performed using R software. Reactome was used to analyze the pathway of immune gene participation. The differentially expressed transcription factors and differentially expressed immune-related genes were extracted from the obtained list of differentially expressed genes, and the transcription factor-immune gene network was constructed. To analyze the relationship between immune genes and clinical traits of bladder urothelial carcinoma, a multifactor Cox proportional hazards regression model based on the expression of immune genes was established and validated. RESULTS: Fifty-eight immune genes were identified to be associated with the prognosis of bladder urothelial carcinoma. These genes were enriched in Cytokine Signaling in Immune System, Signaling by Receptor Tyrosine Kinases, Interferon alpha/beta signaling, and other immune related pathways. Transcription factor-immune gene regulatory network was established, and EBF1, IRF4, SOX17, MEF2C, NFATC1, STAT1, ANXA6, SLIT2, and IGF1 were screened as hub genes in the network. The model calculated by the expression of 16 immune genes showed a good survival prediction ability (p < 0.05 and AUC = 0.778). CONCLUSION: A transcription factor-immune gene regulatory network related to the prognosis of bladder urothelial carcinoma was established. EBF1, IRF4, SOX17, MEF2C, NFATC1, STAT1, ANXA6, SLIT2, and IGF1 were identified as hub genes in the network. The proportional hazards regression model constructed by 16 immune genes shows a good predictive ability for the prognosis of bladder urothelial carcinoma.	bladder
LncRNA DDX11-AS1 Promotes Bladder Cancer Occurrence Via Protecting LAMB3 from Downregulation by Sponging miR-2355-5p.	Background: As a subtype of human genitourinary system cancer, the morbidity of bladder cancer (BC) continues to rise. Because of the high potentiality of cell metastasis, the 5-year survival rate of BC is relatively low. Long noncoding RNAs (lncRNAs) have been verified by a large body of literature to engage in the tumorigenesis of a few cancers. DDX11-AS1 has been elucidated as a malignancy promoter in several cancers; therefore, its mysterious role in BC attracted our interest as being well worth investigating. Aim of the Study: The primary consideration of this article was to clarify the part that DDX11-AS1 plays in the progression of BC. Methods: The expression of DDX11-AS1 in BC was revealed by quantitative real-time polymerase chain reaction. The biological functions of DDX11-AS1 in BC were evaluated through CCK-8 (Cell Counting Kit-8), EDU, TUNEL (TdT-mediated dUTP nick-end labeling), flow cytometry analysis, and Western Blot assays. Luciferase or RNA immunoprecipitation assay was used to investigate the interaction between miR-2355-5p and DDX11-AS1 (or LAMB3). Results: DDX11-AS1 manifested remarkably high level in BC and promoted the malignancy of BC. Moreover, miR-2355-5p was validated to be able to bind with DDX11-AS1 and inhibit cell proliferation in BC. Furthermore, our data suggested that LAMB3 expression was evidently upregulated in BC cells and inversely modulated by miR-2355-5p. Besides, LAMB3 may bind with miR-2355-5p. Ultimately, rescue assays indicated that the restrained development of BC in sh-DDX11-AS1#1-transfected cells could be restored by enforced expression of LAMB3. Conclusion: DDX11-AS1 facilitates the tumorigenesis of BC by the miR-2355-5p/LAMB3 axis.	bladder
Cuprous oxide nanoparticles trigger reactive oxygen species-induced apoptosis through activation of erk-dependent autophagy in bladder cancer.	Cisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer. However, as more than 50% of patients are ineligible for cisplatin-based chemotherapy, there is an urgent need to develop new drugs. Cuprous oxide nanoparticles (CONPs), as a new nano-therapeutic agent, have been proved to be effective in many kinds of tumors. In the present study, CONPs showed dose-dependent and time-dependent inhibitory effects on various bladder cancer cell lines (T24, J82, 5637, and UMUC3) and weak inhibitory effects on non-cancerous epithelial cells (SVHUCs). We found that CONPs induced cell cycle arrest and apoptosis in bladder cancer cells. We further demonstrated that the potential mechanisms of CONP-induced cytotoxicity were apoptosis, which was triggered by reactive oxygen species through activation of ERK signaling pathway, and autophagy. Moreover, the cytotoxic effect of CONPs on bladder cancer was confirmed both in orthotopic xenografts and subcutaneous nude mouse models, indicating that CONPs could significantly suppress the growth of bladder cancer in vivo. In further drug combination experiments, we showed that CONPs had a synergistic drug-drug interaction with cisplatin and gemcitabine in vitro, both of which are commonly used chemotherapy agents for bladder cancer. We further proved that CONPs potentiated the antitumor activity of gemcitabine in vivo without exacerbating the adverse effects, suggesting that CONPs and gemcitabine can be used for combination intravesical chemotherapy. In conclusion, our preclinical data demonstrate that CONPs are a promising nanomedicine against bladder cancer and provide good insights into the application of CONPs and gemcitabine in combination for intravesical bladder cancer treatment.	bladder
Association between metabolic syndrome and recurrence of nonmuscle-invasive bladder cancer in older adults.	BACKGROUND: Nonmuscle-invasive bladder cancer (NMIBC) disproportionately affects older adults who often have coexisting chronic conditions such as metabolic syndrome (MetS). Although prior research suggests that MetS is a risk factor for NMIBC, limited data exists on whether MetS is associated with NMIBC recurrence. Our objective was to evaluate the association between MetS and recurrence in older adults treated for NMIBC. METHODS: We identified 1,485 older (age ≥60 years) NMIBC patients (American Joint Committee on Cancer Stage ≤1) from 2community-based health systems. Using data from the health systems' electronic medical record, MetS was defined as the presence of three of the following: diagnosis codes indicating hypertension, hyperlipidemia, diabetes, or body mass index >30. Follow up time was determined by date of the last follow up in the tumor registry and censored at 10 years. Cox proportional hazards regression of time to recurrence that accounts for the competing risk of death included adjustment for age, sex, smoking status, health system, NMIBC stage/grade, tumor size, and number of specimens with cancer. RESULTS: Overall, 341 patients (23%) met MetS criteria. Median follow up was 5.9 years and 582 patients (39.2%) died. Patients with MetS were more frequently male (84.2%), and mostly current/former smokers (82.6%). By 10 years, 34.1% of the cohort had experienced a recurrence. After accounting for the competing risk of death, there was no association between MetS and time to recurrence (adjusted hazard ratio, 0.88, 95% confidence interval 0.70-1.11, P = 0.28). Patients without MetS had more 0a/low grade recurrences (49.1% vs. 41.4%), though differences were not significant. CONCLUSION: We found no association between MetS and risk of NMIBC recurrence in this large, multisite cohort of older adults with NMIBC. In order to design personalized care for older NMIBC patients, future research is needed to evaluate associations between common chronic conditions and a variety of oncologic outcomes.	bladder
Diagnostic and Prognostic Potential of Biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in Bladder Cancers.	The high occurrence of bladder cancer and its tendency to recur in combination with a lifelong surveillance make the treatment of superficial bladder cancer one of the most expensive and time-consuming. Moreover, carcinoma in situ often leads to muscle invasion with an unfavorable prognosis. Currently, invasive methods including cystoscopy and cytology remain a gold standard. The aim of this study was to explore urine-based biomarkers to find the one with the best specificity and sensitivity, which would allow optimizing the treatment plan. In this review, we sum up the current knowledge about Cytokeratin fragments (CYFRA 21.1), Excision Repair Cross-Complementation 1 (ERCC1), Tumour Protein p53 (Tp53), Fibroblast Growth Factor Receptor 3 (FGFR3), Tumor-Associated Trypsin Inhibitor (TATI) and their potential applications in clinical practice.	bladder
Identifying the mRNAs associated with Bladder cancer recurrence.	OBJECTIVE: To identify the mRNAs associated with bladder cancer (BC) recurrence. METHODS: The transcription profile of GSE31684 including 39 recurrent BC tumor samples and 54 non-recurrent BC tumor samples as well as transcription profile of GSE13507 including 36 recurrent BC tumor samples and 67 non-recurrent BC tumor samples were downlaoded from the Gene Expression Omnibus. Then, the differentially expressed genes (DEGs) were identified using linear models for microarray data (limma) and the intersections of DEGs from the two datasets were further screened. The weighed gene co-expression network analysis (WGCNA) was used to screen the modules related to BC recurrence. Protein-protein interaction (PPI) network analysis was used to analyze the genes interaction. Their functions were predicted by Gene Ontology and KEGG pathway enrichment. Moreover, The Comparative Toxicogenomics Database 2017 update (CTD) was used to search the BC related pathway. The univariate cox regression analysis was used to identify DEGs associated to the recurrence. Kaplan-Meier plots were used to illustrate recurrence free survival time (RFS). RESULTS: A total of 692 intersections DEGs were screened. WGCNA showed that 7 modules (2279 genes) were stable in both the datasets. A total of 169 intersection DEGs were mapped to the 7 modules. There existed 149 interaction relationships among 81 proteins (18 down-regulated and 63 up-regulated DEGs) in the PPI network. Two KEGG pathways including Focal adhesion and ECM-receptor interaction were enriched which were also found in the CTD. The univariate cox regression analysis showed that 3 DEGs (COL4A1, COL1A2 and COL5A1) were significant related to the prognosis. Multivariate cox regression analysis revealed that pathologic_N (N0-N1 vs N2-N3, p= 0.033) were independent prognostic factors for overall survival in patients with BC. CONCLUSION: COL4A1, COL1A2 and COL5A1 could be associated with BC recurrence.	bladder
Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma.	Muscular infiltrating bladder urothelial carcinoma (MIBC) is a highly malignant disease with a poor prognosis. Radical cystectomy is the standard treatment. However, due to surgery and postoperative complications, the quality of life of patients is seriously affected. Therefore, it is increasingly important to find prognostic markers and new therapeutic targets for MIBC. Here, we investigated the expression of PDK1, a key regulator of glucose metabolism, in bladder urothelial carcinoma (BLCA) and its effect on prognosis. The expression pattern of PDK1 was examined by bioinformatics analysis and immunohistochemistry. A total of 101 cases of BLCA were selected for tissue microarrays (TMAs) that contained both tumour and paired normal tissues. We demonstrated that PDK1 expression was correlated with tumour grade and Ki67expression in our TMA cohort (all p values < 0.05). Kaplan-Meier survival analysis showed that patients with MIBC with high PDK1 expression had a worse prognosis than patients with low PDK1 expression (p = 0.016). Multifactor risk analysis showed that increased PDK1 expression was an independent prognostic factor affecting the overall survival of MIBC patients. GSEA showed that the mTOR pathway, HIF pathway, glycolysis, PI3K/AKT/mTOR signalling, etc. were differentially enriched in the PDK1 high expression phenotype. Hence, PDK1 may be a prognostic and therapeutic target for MIBC.	bladder